NEURAL DEVELOPMENT--INTERCELLULAR AND HUMORAL CONTROL

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The five participating research groups share a common interest in understanding the importance and mechanisms of intercellular and hormonal signals that regulate the postembryonic development and plasticity of neurons. Growing collaboration among these groups over the past eight years and increasing mutual focus on the mechanisms that control developmental plasticity within the nervous system have led to the emergence and continued success of this Program Project. Among the research areas represented by these laboratories are; the roles and mechanisms of short-distance and contact-mediated intercellular influences in neural development; hormonally regulated, postembryonic differentiation and remodeling of motor neurons and interneurons; ultrastructural and physiological aspects of synapse formation in d enveloping neural systems; the role of glial cells in the development of organized neuropil in the central nervous system; and molecular mechanisms of steroid hormone regulation of neuronal development. The participants will mount multidisciplinary, highly collaborative investigations of mechanisms underlying hormonal and trans-cellular regulation of the survival and development of nerve cells during postembryonic life. Specifically, the five component projects include: (1) molecular mechanisms of gene regulation by steroid hormones and characterization of steroid-sensitive genes; (2) morphological and biophysical development of CNS glial cells and their regulation by trans-cellular interactions; (3) steroid-hormonal regulation of development of identified motor neurons in primary cell culture; (4) molecular and genetic analysis of steroid hormone responsive genes and their roles in CNS development; and (5) cellular interactions and molecular mechanisms regulating the development of a primary olfactory center. All of the proposed studies are based on the use of invertebrate model systems that are economical, readily available, and experimentally favorable. Because they have been extensively studied by many investigators, including the participants in this program project, the insect preparations to be used in the proposed studies are especially well understood and favorable for these experiments. Specifically, Manduca offers excellent access to physiological and hormonal mechanisms, whereas Drosophila offers a powerful array of molecular and genetic approaches. The basic mechanisms of development have been conserved during evolution. We expect, therefore, that information obtained in these projects about neural and muscular development in insects will illuminate related phenomena in other animals including human beings.